The role of dynamically correlated conformational equilibria in the folding of macromolecular structures. A model for the design of folded dendrimers

This review explores how the occurrence of synchronized conformational fluctuations within a folded macromolecular structure contributes to its structural and functional properties. These fluctuations interconvert multiple conformational states that are separated by small energetic barriers. Internal motions that occur on very short time and length scales in proteins greatly influence processes such as ligand binding, catalysis, allostery and thermodynamic stability. Furthermore, recent evidence suggests that the residual conformational fluctuations are correlated within the folded structure of proteins. These observations suggest that the mechanism by which the residual motions contribute to the thermodynamic stability of proteins is related to the chiral amplification phenomenon observed in helical polymers and supramolecular assemblies. In these synthetic systems, extensive theoretical and experimental studies have demonstrated that conformational synchronization that occurs over extended distances amplifies small energetic differences relating conformational states leading to highly stable folded materials. The effect of these synchronized fluctuations on the conformational properties provides a model for the design of dendrimers that adopt folded conformations and amplify chiral structural perturbations.